6. Pathogenesis of asthma 1 Flashcards
What is asthma?
- A chronic inflammatory disease of the lung.
- It is common and affects around 300 million people worldwide.
- Around 250,000 asthma-related death annually.
What does asthma cause?
- Cells of the immune system act with epithelial cells cause tissue damage.
- Bronchial hyper reactivity (BHR)
- Mucus overproduction
- Airway wall remodelling
- Airway narrowing.
What are the common symptoms of asthma?
Repeated episode of wheezing, shortness of breath and chest tightness.
How are histological changes in the asthmatic lung studied?
- Tissue section of the medium airway.
- Stain the tissue with Movat’s pentachrome.
What histological changes occur in the asthmatic airway?
- Hyperplasia of the epithelium
- Hypersecretion of mucus
- Thickening of the basement membrane
- Increased smooth muscle volume
What do all the histological changes in the asthmatic airway cause?
- They cause significant narrowing of the airway.
- This compromises lung function.
What are the 2 traditional types of asthma?
- Allergic asthma
- Non-allergic asthma
What is allergic asthma?
- The more prevalent type of asthma.
- 50% of adult asthma is allergic asthma.
- the majority of childhood asthma is allergic asthma.
- There must be an IgE allergic reaction to an aero-antigen or another antigen that drives asthma.
What is non-allergic asthma?
- It is mostly found in adults
- There no presence of IgE.
Why was the classification of asthma reconsidered?
Due to its heterogeneity.
What factors are considered in the way of classifying asthma now?
- Clinical presentation
- Age of onset
- Genetic susceptibility
- Response to environmental factors
- Degree of inflammation/BHR
- Degree of tissue remodelling
- Response to therapy
- Prognosis
What is the prevalence of asthma in the UK?
- Used data from 2007
- Samples were taken from the same place and with the same method to rule out confounding factors.
- Asthma prevalence has increased over time in the UK.
- Diagnosis of asthma has reached a plateau.
- Currently it is estimated that over 12% of the population in the UK has been diagnosed with asthma.
What causes asthma?
- Host genetic risk factors
- Environmental risk factors including susceptibility and precipitating factors.
- There is complex interplay between these factors that decides the development and severity of asthma.
What is the genetic heritability rate of asthma?
35-95%
What are susceptibility environmental risk factors in asthma?
- These are things that act on the genetic predisposition to asthma to turn you from a healthy person to an asthmatic person.
- They act on the genetic risk.
What are precipitating environmental risk factors in asthma?
These are things that will set off an asthma attack.
What kind of inheritance does asthma show?
- 1 or 2 parents with asthma or another allergic disease increases risk.
- No 1 mutation causes asthma
- Asthma is polygenic so lots of genes contribute to the overall susceptibility profile of a person.
What are the asthma susceptibility loci?
- Gene expressed in the airway
- Genes that regulate CD4 Th2, ILC2 and type 2 immune responses.
- Other genes
What genes expressed in the airway can effect asthma susceptibility?
- Chemokines like CCL5
- Antimicrobial peptides like DEFB1
- Epithelial barrier protein like FLG
What genes that regulate Th2 CD4 T cells and other type 2 responses can effect asthma susceptibility?
- Transcription factors like GATA3, RORa and STAT3.
- Cytokines: IL4, IL5, IL10, IL13 and IL33
- Cytokine receptors like IL4R and IL5R
What genes that regulate other functions can effect asthma susceptibility?
- Proteinase or proteinase inhibitors like ADAM33
- Signalling proteins like Notch4 and SMAD3
What can we gain an idea of by looking at the asthma susceptibility loci?
We can start to build up an idea of the pathogenesis of asthma.
Examples of environmental risk factors - susceptibility
- Indoor and outdoor allergens
- Occupational sensitisers like solvents
- Tobacco smoke (active or passive)
- Air pollutants
- Respiratory infections (mostly viral)
- Parasitic infections
- Family size
- Diet and drugs
- Obesity
Examples of environmental risk factors - Precipitating
- Overlaps with susceptibility list.
- Indoor and outdoor allergens.
- Air pollutants
- Tobacco smoke (active or passive)
- Exercise and hyperventilation
- Respiratory infections (mostly viral)
- Weather changes like thunderstorms
- Sulphur dioxide (a common preservative)
- Extreme emotional expression